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Hepcidin mediated iron homoeostasis as immune regulator in visceral leishmaniasis patients
Author(s) -
Singh Bhawana,
Singh Siddharth Sankar,
Sundar Shyam
Publication year - 2019
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12601
Subject(s) - hepcidin , ferroportin , immune system , biology , transferrin , immunology , transferrin receptor , homeostasis , dmt1 , inflammation , endocrinology , biochemistry , transporter , gene
Summary Aim Iron is key ingredient for immunosurveillance and host‐pathogen interaction. Intracellular pathogen steals the iron from the host, but how parasite orchestrates iron acquisition and affects immune responses remains controversial. We aimed to study the iron homoeostasis in visceral leishmaniasis (VL) and its influence on immune machinery. Methods and Results This study was performed on purified monocytes and T cells, peripheral blood mononuclear cells and splenic aspirates for transcriptional analyses of iron homoeostasis (hepcidin, DMT1, transferrin receptor, ferroportin) and immune modulations (IFN‐γ, HLA‐DR, IL‐10, iNOS, IL‐6). Serum/plasma was used for determination of iron, total/transferrin iron‐binding capacity and anti‐leishmania antibody titres in cases. We report that VL‐induced perturbation in iron homoeostasis may cause immune dysfunctions. VL cases had decreased iron uptake by transferrin‐dependent and transferrin‐independent routes while elevated hepcidin, degraded sole iron exporter ferroportin. Therefore, it appears that perturbation in iron homoeostasis has essential role in HLA‐DR mediated antigen presentation and innate armoury by downregulating iNOS as well as altering IFN‐γ, IL‐6 and IL‐10 profiles. Conclusion The iron homoeostasis by hepcidin can serve as one of the crucial determinants for regulating immune cell signalling; therefore, targeting iron metabolism, specifically hepcidin alone or in combination with agonists, can serve to clear infection.